@article {1653576,
	title = {Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer{\textquoteright}s-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia},
	journal = {Acta Neuropathol Commun},
	volume = {10},
	number = {1},
	year = {2022},
	month = {2022 Sep 08},
	pages = {136},
	abstract = {Single cell RNA sequencing studies identified novel neurodegeneration-associated microglial (MGnD/DAM) subtypes activated around cerebral amyloid plaques. Micro-RNA (miR)-155 of the TREM2-APOE pathway was shown to be a key transcriptional regulator of MGnD microglial phenotype. Despite growing interest in studying manifestations of Alzheimer{\textquoteright}s disease (AD) in the retina, a CNS organ accessible to noninvasive high-resolution imaging, to date MGnD microglia have not been studied in the AD retina. Here, we discovered the presence and increased populations of Clec7a+ and Galectin-3+ MGnD microglia in retinas of transgenic APPSWE/PS1L166P AD-model mice. Conditionally targeting MGnD microglia by miR-155 ablation via the tamoxifen-inducible CreERT2 system in APPSWE/PS1L166P mice diminished retinal Clec7a+ and Galectin-3+ microglial populations while increasing homeostatic P2ry12+ microglia. Retinal MGnD microglia were often adhering to microvessels; their depletion protected the inner blood-retina barrier and reduced vascular amyloidosis. Microglial miR-155 depletion further limits retinal inflammation. Mass spectrometry analysis revealed enhanced retinal PI3K-Akt signaling and predicted IL-8 and Spp1 decreases in mice with microglia-specific miR-155 knockout. Overall, this study identified MGnD microglia in APPSWE/PS1L166P mouse retina. Transcriptional regulation of these dysfunctional microglia mitigated retinal inflammation and vasculopathy. The protective effects of microglial miR-155 ablation should shed light on potential treatments for retinal inflammation and vascular damage during AD and other ocular diseases.},
	keywords = {Alzheimer Disease, Animals, Disease Models, Animal, Galectin 3, Inflammation, Lectins, C-Type, Membrane Glycoproteins, Mice, Mice, Transgenic, Microglia, MicroRNAs, Phenotype, Phosphatidylinositol 3-Kinases, Receptors, Immunologic},
	issn = {2051-5960},
	doi = {10.1186/s40478-022-01439-z},
	author = {Shi, Haoshen and Yin, Zhuoran and Koronyo, Yosef and Fuchs, Dieu-Trang and Sheyn, Julia and Davis, Miyah R and Wilson, Jered W and Margeta, Milica A and Pitts, Kristen M and Herron, Shawn and Ikezu, Seiko and Ikezu, Tsuneya and Graham, Stuart L and Gupta, Vivek K and Black, Keith L and Mirzaei, Mehdi and Butovsky, Oleg and Koronyo-Hamaoui, Maya}
}
